Mitosis

Mitosis

Prior to you ever seeing the chromosomes, the DNA has been replicated. So, each "chromatid" is actually a complete, new chromosome ready to be passed to the daughter cell.

Prior to mitosis, the centrioles (two tubular-based structures also called "microtubule organizing center," or MTOC, and also known as basal bodies and centrosomes), have been duplicated and each has migrated to opposite sides of the nucleus, where they are now called the "spindle-pole body." Lot of names for one structure.

The "centromere" refers to the structure at the little constriction in the chromosomes…not necessarily in the "center." Centromere DNA to most molecular biologists refers to the DNA that has a specific sequence that interacts with specific proteins that comprise the rest of the structure.

The kinetochore refers to the complete structure with proteins.

Microtubules grow from the spindle-pole body (SPD) in all directions. The ones that fail to be stabilized (see below), will suddenly shorten if the terminal tubulin dimers hydrolyze their GTP.

Microtubules can be stabilized in one of two ways: they can land at a kinetochore and attach there, or line up along microtubules from the other pole. These non-kinetochore microtubules and motors associated with them will push the SPDs apart, as seen at 3:30 in the video.

Kinetochore microtubules interact with motor structures that try to pull the chromatids apart. But, they are held together by a complex of proteins, the principle one is called "securin."

A complex of proteins known as "anaphase-promoting complex" or APC, is inhibited prior to anaphase by a cyclin/cdk complex.

At anaphase, the cyclin above is destroyed, which activates an enzyme known as "separase" (guess what that causes). It cuts securin and the chromatids separate.

This figure was provided by Kevin Sullivan via research-gate and is from the following paper.

Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling

March 2003Cell 112(4):407-21

DOI: 10.1016/S0092-8674(03)00115-6

Authors: Don Cleveland, Yinghui Mao and Kevin Sullivan

It shows many of the players. Notice that dynein, a motor protein on microtubules that "walks" toward the minus, or MTOC end of the tube, is connected to the kinetochore by a protein called "dynactin." It is trying to walk the chromosome up to the SPD. To get to metaphase, tubules on both side of the kinetochore pull toward their respective poles. They are roughly equal in strength and end up in the center at the "metaphase plate." When separase activates, the chromatids separate and the tubules shorten, as the dynein walks them up toward the poles.

The regulation is actually rather complex. Rohit is probably thinking of reasons this cannot work. It does. There are some fairly complex networked feedback pathways that keep it working.